comprehensive assessment of morphometric, functional, biomechanical and biological interactions between atherosclerotic plaque and platelets within the stenosed coronary artery

Conditions: Chronic Coronary Syndrome; Atherosclerosis

Summary: the main objective of the present study is to verify, in vivo, whether shear forces computed solely based on coronary angiography and computational fluid dynamics (cfd) techniques are associated with the biomarkers indicating the prothrombotic tendency of circulating blood in situ - distally and proximally to the coronary stenosis. the study will prospectively assess the relationship between i) the value and distribution of shear rate and shear stress (ss) estimated using three-dimensional angiography and cfd techniques, and ii) atherosclerotic plaque characteristics as assessed by optical coherence tomography (oct), iii) functional parameters of diseased vessels assessed by vessel fractional flow reserve (vffr), and iv) in situ platelet activation, as expressed by platelet-derived microvesicles (pmvs) and small extracellular vesicles (sevs), platelet aggregometry and other serum prothrombotic or inflammatory biomarkers sampled within the coronary artery.

the biomechanical forces, including shear rate and shear stress exerted by circulating blood on the coronary wall and on circulating blood elements have been reported to contribute to the processes of plaque destabilization and thrombosis. reliable estimation of shear (shear rate and shear stress) acting in vivo within the coronary artery has now become possible using imaging data and computational fluid dynamics techniques. the changing microenvironment of the plaque has a crucial role in the biochemical processes involved in remodeling the plaque itself. in this prospective, single-center study a total of 105 patients will be enrolled presenting with chronic coronary syndrome and angiographically confirmed coronary stenosis (30% - 90%) amenable to oct imaging (according to the operator's judgment). the groups will be assessed at the time of angiography with: * oct examination for precise evaluation of plaque morphology within the coronary stenosis * computational fluid dynamics with vffr and estimation of value and distribution of shear rate and shear stress * impedance aggregometry-based platelet reactivity * single-particle high-resolution flow cytometry analysis of platelet-derived microvesicles and small extracellular vesicles (sevs) as well as additional platelet activation (p-selectin, annexin-v) and inflammatory biomarkers * proteomic and metabolomic characterization - in the subset of patients biomarker assessment will be done in the blood sampled directly from coronary artery (proximal and distal segment).

Eligibility criteria:
inclusion criteria: * chronic coronary syndrome * angiographically confirmed coronary stenosis (30% - 90%) * amenable to oct imaging exclusion criteria: * cardiogenic shock * st-segment elevation or non-st-segment elevation myocardial infarction * active bleeding * left main coronary artery disease * multivessel disease * lesions located at a distance ≤3 mm from the ostium of the vessel * thrombocytopenia * previous coronary artery bypass grafting * previous coronary intervention with stent implantation or balloon angioplasty * previous use of novel oral anticoagulants or vitamin k antagonists

Keywords: optical coherence tomography vffr shear rate impedance aggregometry shear stress proteomic metabolomic computational fluid dynamics prothrombotic platelet vulnerable plaque